Pfizer Confidential 1

アジアにおける開発体制-企業の立場から-

Tomoko Hirohashi. PhD

Director, Clinical Research, Oncology, Pfizer Japan

Miho Yamamoto, Kae Nakashima, Katsushi Namazu

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Background

• Recently clinical development in China is dramatically growing

• In addition, basic research and translational research are also advancing in other Asian countries such as China

– China’s 2016-2020 5-year plan prioritizes bio R&D as a key focus area; 2016 allocated 30% of social development budget (Justin C et.al. NEJM. 2014)

• Now is the time to think again about Japan’s position in drug development and where should we head

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Source：Citeline Chinese Government initiates significant regulatory reforms as “ The Innovation Opinion” containing 36 specific revisions

(State Council Doc. No42)

• Reforming clinical trial management• Accelerating drug device review and approval

process• Balancing development of innovative drugs

and generic drugs• Life-cycle management of drugs and devices• Enhancing drug and medical device review and

enforcement force• Implementation of the innovation opinion and

coordination among the relevant administrative agencies

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State CouncilDoc. 44

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Clinical Research

Basic and Translational Research

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Clinical Research

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Clinical Research: Organization and Number of Trials

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All DA Oncology

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China

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l• ~340 members in Dev-Japan vs 160 members in Dev-China(excluding direct global lines) • Clinical: 50 members in Japan vs 24 members in China

Japan has great advantages over China so far; China has been struggling to participate into global studies

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Japan has a great advantages over China “ So Far”

<Advantage>：“Matured”

• Regulatory advantage

– Necessity of Phase 1 before registration trial

• Well-organized Japan affiliate (Established reliance from global)

– Studies led by Pfizer Japan had “fastest record“ among Project A (project buy-up to protocol finalization and FSFV)

• Sufficient capability at study sites

– Sufficient experience, including Phase 1 (DLT evaluation etc)

– Speedy start up and commitment (contribution to short cycle time)

– GCP compliance and quality

• Strong leadership of Japan KOLs in certain areas

<Disadvantage>: “COSTLY”

• Highest cost for FTE (both internal and CRO cost)

• Less performance per CRA/site than other Asian countries

• Post marketing requirement (PMS, all case survey etc)

• Regional Specific/Strict requirement for IVD and CDx

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China has been struggling to participate in global studies

<Advantage>

• Huge potential of enrollment

• Performance per a CRA/site is high

• Participation into global registration study using Japanese PK & safety data

<Disadvantage>

• Slow study start up

• Quality issues (Field inspection detected 28.1% did not meet ALCOA+CCRA)

• Less experiences of Phase 1 (DLT evaluation)

• Biospecimen assay (difficulty to implement companion diagnostics)

One of the KEY focus area of “ The Innovation Opinion” is “Reforming clinical trial management” , which could substantially reduce delays in the approval of clinical trial applications (Nov 6th, 2017: www.cov.com)

Intensive training for CRA is requested by the CFDIThe CFDI is expanding and hiring more staff, and the training is more standardized and consistent (J Evid Based Med. 2018; 11:3-6)

Global accepts “Dare To Try” for CHINA

CFDI:Center for Food and Drug InspectionsACLOA: Attributable, Legible, Contemporaneous, Original and AccurateCCEA: Complete, Consistent, Enduring and Available

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Now most pharma have strong interest in China

Made the call! China Regulation Reform (SC No. 44/42)

• Modernization and standardization to global norms of regulation

• Has shifted from emerging market to innovative drug/health

– Japan is now strengthening use of generics in priority prefectures

• Implemented “conditional approval” for innovative drugs

48 products selected as “ Fast Track”

Palbociclib was approved in Aug 2018 with 2 years acceleration based on Chinese PK study only

• (Will?) improve medical device regulations and harmonize them with international practices

Global organization proactively includes China into ongoing/future global registration studies!

1) http://www.ey.com/Publication/vwLUAssets/ey-life-sciences-report-asia-march-2017/$FILE/ey-life-sciences-report-asia-march-2017.pdf

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Considerations

JAPAN

CHINA

Advantages• Highest CAGR• Huge potential of accrual• Changing regulatory

environments• Big data• Digital health

Concerns• Quality (improving!!*)• Custom compliance (import

pricing and adjustment)

Concerns• Highest FTE (CRO cost)• New drug pricing policy• All case survey• PMS

Advantages• Speed of SSU• Plenty of successful

experiences in clinical trials (both internal and external)

*J Evid Based Med. 2018; 11:3-6

CAGR: Compound average growth rate

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What should we do??

In China, simultaneous development/submission/approval would become standard like current Japan

Japan needs more cost efficient study management as a first step

– More disruptive idea using IT, digital platform etc

• Risk Based Monitoring

• eSource, eICD etc..

• More efficient PMS and all case survey to reduce overall cost of drug development

– More “patients centric approach”

As a next step, Japanese must become global players in global organization, not considering only Japan but also the globe

It is a high time to be a real global role from a region

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Basic and Translational ResearchPartnering with Academia

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Basic/Translational Research Collaboration/Partnering Model

• One on One Collaboration

• CTI (Center for Therapeutic Innovation), “a Joint Project”

• Collaboration through the research center consisted of several academia and Pfizer to conduct drug R&D(from the stage of idea creation to a first in human study)

• ITEN (Innovative Target Exploration Network)

• Partnering model with selected academic institutions and PIs for early-stage “research project” that have the potential to deliver innovative therapeutic targets

PI: Principle investigator

Collaboration with multiple institutions/researchers become one of standard partnering models.Global is now very interested in collaboration with Asian countries.

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Summary

• Number of clinical trials in Japan is still higher than China

• However, huge investment to China has been committed due to highest CAGR, high potential of accrual, change of regulatory environments etc.

• Japan performance is good in study start up and quality, however needs to improve study cost (CRO/CRA cost), performance per CRA/site using innovative IT tools; more patient centric approaches should be promoted proactively

• In addition, Japan affiliates need to expand it’s role

– Become a global role (more global assignment of Japanese)

– Japan clinical members should be involved in open innovation activities with daily communications not only on clinical but also on basic/translational research topics

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